This is an amended application for a program that emphasizes research training and investigations of the fundamental biochemical and biophysical events that underlie the cellular alterations characteristic of neoplastic processes. Training is provided by faculty from the Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health;the Sidney Kimmel Comprehensive Cancer Center of the Johns Hopkins Medical Institutions;and other departments of the School of Public Health. The program, which is designed to support nine predoctoral and four postdoctoral trainees, uses laboratory research integrated with formal course work to provide training in the biochemical, biophysical and molecular biological approaches required to address critical problems in cancer biology. To further ensure that trainees acquire and maintain a clear and comprehensive understanding of the cancer problem, all present and past trainees will be required each year to attend and participate in a cancer biology seminar series and a biweekly cancer journal club. Predoctoral trainees will be admitted to the program only after they have demonstrated a strong academic and laboratory rotation record and have selected a thesis dissertation project with a clear relevance to the cancer problem. Outstanding postdoctoral candidates will be recruited who have demonstrated a strong interest to pursue research in the area of cancer biology. The training faculty are all productive and have external funding necessary to support the investigations of the trainees. Major research themes, which are relevant to and focus on the cancer problem, include: apoptosis and programmed cell death;gene silencing and epigenetic changes to the genome;cellular remodeling and associated regulatory circuits;protection from environmental damaging agents;and structure and function of DNA repair systems. In the past this program has attracted talented young trainees, most of whom remain in science and many of whom have achieved distinction in the field of cancer biology and its underlying disciplines. The proposed program will continue to bring trainees into the field and equip them for productive careers in cancer research.